This study proposes the application of a newly developed system for modeling the microcirculatory responses to experimentally induced changes in physiology, to injury and to disease. The system consists of television microscopy by fiber optic transillumination of the lingual frenulum of the dog. Videotape recording and instant recovery of permanent visual images are central to the innovative application of this technology. In a dog model using hypovolemic shock we have been able to analyze the in vivo microcirculatory behavior of red blood cells and platelets while they circulate through the microvessels of living uninjured tissue of healthy animals and to correlate this with their behavior in suitable in vitro tests done simultaneously. Then after the experimentally imposed insult, the system allows objective and quantitative demonstration of both in vivo and in vitro responses to the altered pathophysiologic state of the subject. This system is especially well suited for the study of the in vivo and in vitro behavior of erythrocytes and platelets and the responses of small blood vessels and tissue perfusion in dogs rendered diabetic using alloxan and pancreatectomy. The initial goal of this study will be to develop and to carry out an experimental series using this modeling system to study the dynamics of the microcirculation, the responses of and changes in the small blood vessels, erythrocyte aggregation, and platelet stickiness and aggregation in diabetes. Subsequent goals will be to follow these parameters as diabetes progresses in our canine subjects over a period of years and to observe for arrest or reversal of microcirculatory abnormalities with insulin therapy.